Park Yong Ho, Lee Sang Un, Ferens Witold A, Samuels Sparrow, Davis William C, Fox Lawrence K, Ahn Jong Sam, Seo Keun Seok, Chang Byoung Sun, Hwang Sun Young, Bohach Gregory A
Department of Microbiology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea.
J Vet Sci. 2006 Sep;7(3):233-9. doi: 10.4142/jvs.2006.7.3.233.
We previously demonstrated that stimulation of bovine peripheral blood mononuclear cells (PBMCs) with staphylococcal enterotoxin C (SEC), led to an inversion of the CD4(+):CD8(+)T cell ratio and generation of an atypical CD8(+)T cell subpopulation expressing CD26. In the present study, we examined T cell apoptosis and proliferation profiles of PBMC subpopulations in cultures stimulated with SEC. Unlike when stimulated with concanavalin A, nucleic acid synthesis in bovine PBMC cultures stimulated with SEC was low during the first four days but increased greatly on day 5. In contrast, nucleic acid synthesis in human PBMC cultures stimulated with SEC increased continuously. To investigate the mechanism of delayed bovine T cell proliferation, various cell phenotypes were monitored. The inversion of the bovine CD4(+):CD8(+)T cell ratio in PBMC cultures stimulated by SEC was associated with higher proliferation and lower apoptosis of CD8(+)T cells compared to CD4(+)T cells. The mRNA levels for interleukin (IL)-4 and IL-13 were sustained over 4 days but IL-12 mRNA levels dropped to background on day 2. These data suggest that SEC induces a prolonged Th-2- biased microenvironment, and together with the inversion of the bovine CD4(+):CD8(+)T cell ratios in bovine PBMC cultures with SEC, may in part explain the inability of the mammary immune system to establish an effective response to Staphylococcus aureus infections.
我们之前证明,用葡萄球菌肠毒素C(SEC)刺激牛外周血单个核细胞(PBMC),会导致CD4(+):CD8(+)T细胞比例倒置,并产生表达CD26的非典型CD8(+)T细胞亚群。在本研究中,我们检测了SEC刺激培养的PBMC亚群的T细胞凋亡和增殖情况。与用刀豆蛋白A刺激时不同,SEC刺激的牛PBMC培养物中的核酸合成在前四天较低,但在第5天大幅增加。相比之下,SEC刺激的人PBMC培养物中的核酸合成持续增加。为了研究牛T细胞增殖延迟的机制,监测了各种细胞表型。与CD4(+)T细胞相比,SEC刺激的PBMC培养物中牛CD4(+):CD8(+)T细胞比例倒置与CD8(+)T细胞的较高增殖和较低凋亡相关。白细胞介素(IL)-4和IL-13的mRNA水平持续4天,但IL-12 mRNA水平在第2天降至背景水平。这些数据表明,SEC诱导了一个长期的以Th-2为主的微环境,并且与SEC刺激的牛PBMC培养物中牛CD4(+):CD8(+)T细胞比例的倒置一起,可能部分解释了乳腺免疫系统无法对金黄色葡萄球菌感染建立有效反应的原因。